Abstract: Huntington's disease (HD) is a fatal neurodegenerative disease for which no therapy has been proven to delay onset or to slow progression of the disease. The development of therapies is challenged by lack of clear understanding of disease mechanisms and limited availability of biomarkers which could be used to monitor the effectiveness of therapies. MicroRNAs (miRNAs) are short non-coding RNA molecules which are appealing for biomarker discovery and development because of their relative abundance and remarkable stability in biofluids. We hypothesize that, miRNA markers associated with neurodegeneration in HD brain can be detected in the CSF and plasma of HD patients and have preliminary data demonstrating disease-related miRNA signatures in both biofluids. Here we propose examining the miRNA signatures present in concurrent CSF and plasma samples from HD patients and comparing them with each other and with miRNA changes in postmortem HD brain. Our goal is to understand the inter-relationships of the plasma and CSF miRNome in HD patients and the overlap of these with brain miRNA. We hope to identify candidate plasma and CSF markers that could correlate with neurodegeneration in brain.